Hepatocellular Adenoma Risk Factors of Hemorrhage: Size Is Not the Only Concern!

Julien, Céline; Lebail, B.; Touhami, Kevin Ouazzani; Frulio, Nora; Blanc, Jean‐Frédéric; Adam, Jean‐Philippe; Laurent, Césari; Balabaud, Charles; Bioulac‐Sage, Paulette; Chiche, Laurence

doi:10.1097/sla.0000000000005108

Cited by 22 publications

(22 citation statements)

References 24 publications

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“…The published series are too small to enable comparison of the percentages of the different subtypes between men and women; however, in our experience, the subtypes with the highest percentages in men are b‐HCAs and b‐IHCAs with exon 3 non‐S45 mutations 79 …”

Section: Hca In Particular Clinicopathological Contextsmentioning

confidence: 74%

“… * Percentages of cases and F/M ratios are derived from Julien et al 79 ; the percentage of shHCA is based on ASS1 immunostaining; other teams are using PTGDS 1 …”

Section: Hca Classificationmentioning

confidence: 99%

“…Clinical bleeding is defined as severe when it requires intensive care, and moderate when there are clinical or radiological bleeding symptoms 79 ; histological bleeding is defined as haemorrhage incidentally found at microscopic examination 1 . All HCAs carry a risk of clinical bleeding, and the main risk factor is traditionally reported to be the size (>50 mm), 1,8 but bleeding has been reported for HCAs as small as 35 mm 73,80 .…”

Section: Hca Complicationsmentioning

confidence: 99%

“…Exophytic growth and visualisation of intratumoral arteries by the use of magnetic resonance imaging (MRI) are other risk factors 73 . Recent studies showed shHCA, b‐HCA exon 7/8 mutation subtypes, 1,79 both even if smaller than 50 mm, and chronic alcohol consumption as independent risk factors 79 . HCA can disappear after bleeding or arterial embolisation 75 .…”

Section: Hca Complicationsmentioning

confidence: 99%

“…However, HCA of <50 mm seems to have a minimal risk of growth, 110 and haemorrhage was reported to be rare and associated with HCA of ≥65 mm, although it can be fatal 111 . Bleeding can be a major complication close to term and in the postpartum period in patients with b‐HCA with exon 3 S45 and exon 7/8 mutations 79 . As yet, association of these complications with specific HCA subtypes during pregnancy is not established, because of limited data, partly because the diagnosis of HCA during pregnancy is not tissue‐based.…”

Section: Hca In Particular Clinicopathological Contextsmentioning

confidence: 99%

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Hepatocellular adenoma: what we know, what we do not know, and why it matters

et al. 2022

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Hepatocellular adenoma: what we know, what we do not know, and why it mattersIn the last two decades there has been significant progress in research on and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties, and identifying still unknown aspects of HCA. We discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of b-cateninmutated HCAs. The major complications of HCAs, i.e. bleeding and malignant transformation, are considered, including the dilemmas of atypical and borderline lesions. HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries, are also discussed. The natural history of the different HCA subtypes in relation to age, sex and risk factors is a feature that is still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumour, a multicentre and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programmes with which to identify, classify and manage HCAs, focusing on several aspects, e.g. aetiology, underlying liver disease, complications, regression, and growth. Updating what we know and identifying and addressing what we do not know matters for optimal patient management.

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Section: Hca In Particular Clinicopathological Contextsmentioning

confidence: 74%

“… * Percentages of cases and F/M ratios are derived from Julien et al 79 ; the percentage of shHCA is based on ASS1 immunostaining; other teams are using PTGDS 1 …”

Section: Hca Classificationmentioning

confidence: 99%

Section: Hca Complicationsmentioning

confidence: 99%

Section: Hca Complicationsmentioning

confidence: 99%

Section: Hca In Particular Clinicopathological Contextsmentioning

confidence: 99%

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Hepatocellular adenoma: what we know, what we do not know, and why it matters

et al. 2022

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Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation

Demory

Péron²,

Caldéraro

et al. 2022

Hepatology

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Background and Aims: The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen‐based contraception discontinuation. Approach and Results: We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen‐based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen‐based contraception for a median of 12 years. Thirty percent of patients had at least one HNF1A‐inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of β‐catenin (bHCA). Twenty‐one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages < 37 years old (p = 0.004) and HCA > 5 cm at imaging were independently associated with symptomatic bleeding (p = 0.003), whereas a bHCA was associated with malignant transformation (p < 0.001). After a median follow‐up of 5 years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression (p < 0.0001) and weight gain with progression (p = 0.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29–4.19; p = 0.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients (p = 0.003). Conclusion Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.

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Clinical relevance of subtyping CTNNB1‐mutated hepatocellular adenomas: Different risk patterns according to the mutation type

Bioulac‐Sage,

Sempoux,

Gouw

et al. 2024

Liver International Communications

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Background and AimsBeta‐catenin‐activated hepatocellular adenomas (b‐HCA) with exon 3 (ex3) non‐S45, ex3 S45 or ex7/8 mutations display different glutamine synthetase (GS)‐immunostaining patterns; the latter two show a GS‐positive/CD34‐negative rim contrasting with diffuse CD34 in the HCA core. Our objective was to determine whether discriminating the three b‐HCA mutation subtypes is clinically relevant.MethodsWe analysed the clinicopathological data of the three b‐HCA subtypes (37 resected cases) and compared it with the corresponding subtypes of beta‐catenin‐activated inflammatory HCA (b‐IHCA, 40 cases).ResultsThe mean age of b‐HCA ex7/8 and ex3 S45 were 25.9 and 27.3 years respectively. Clinical bleeding occurred in 67% and 63%, including five cases of pregnant women; malignant transformation was not observed in these two subtypes. The mean age of the b‐HCA ex3 non‐S45 subtype (41 years) was significantly higher; clinical bleeding occurred in 14% while all cases contained malignancy. Such differences in age and clinical complications were not found in the b‐IHCA subtypes. Additionally, we found abnormal vessels in b‐HCA ex3 S45 and ex7/8, near the GS+/CD34− rim, which was not seen in ex3 non‐S45. These vessels can function as an adjunct to discriminate between the b‐HCA subgroups.ConclusionIn our series, b‐HCA ex7/8 and ex3 S45 patients are significantly younger and have higher clinical bleeding risk than b‐HCA ex3 non‐S45 patients who have a higher malignant risk. Hence, in b‐HCA, due to the differences in clinical complications, it is clinically relevant to identify all three subtypes individually.

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Hepatocellular Adenoma Risk Factors of Hemorrhage: Size Is Not the Only Concern!

Cited by 22 publications

References 24 publications

Hepatocellular adenoma: what we know, what we do not know, and why it matters

Hepatocellular adenoma: what we know, what we do not know, and why it matters

Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation

Clinical relevance of subtyping CTNNB1‐mutated hepatocellular adenomas: Different risk patterns according to the mutation type

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